D-tagatose (TAG), also known as (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one or Naturlose®, is a ketohexose, isomer of fructose and functional sweetener. It is a white anhydrous crystalline solid and has a molecular weight of 180.16 and empirical formula of C6H12O6. It is about 92% as sweet as sucrose and has been reported for use as a nutritive or low-calorie sweetener. Only about 25% of TAG ingested in humans is absorbed into the bloodstream. TAG is a naturally occurring molecule found in heated dairy products, including sterilized and powdered cow's milk, hot cocoa, various cheeses and yogurt, although TAG can also be chemically manufactured. Various patents disclose information regarding TAG and its conventional uses.
U.S. Pat. No. 6,991,923 discloses a process for manufacturing TAG that includes hydrolyzing lactose to galactose and glucose, isomerizing galactose to tagatose and then chromatographically separating the compounds and recycling any unconverted compounds. TAG supplies 1.5 kcal/g of energy (as compared to 4 kcal/g from sucrose), in large part because TAG is incompletely absorbed by the small intestine. Some uses of TAG include as a sweetener in diet beverages at concentrations up to 1%, light ice creams or yogurts at concentrations up to 3%, and regular or dietetic hard candies at levels up to 15%.
U.S. Pat. No. 4,786,722 discloses a process for the preparation of a sweetened edible formulation in which the sweetening agent is less caloric than sucrose which includes the step of mixing a foodstuff with an amount sufficient to sweeten the foodstuff with TAG.
U.S. Pat. No. 5,356,879 discloses a method for preventing the formation of advanced glycosylation end-products in a mammal including administering to said mammal an effective amount of TAG.
U.S. Pat. No. 5,447,917 discloses TAG as an anti-hyperglycemic agent.
U.S. Pat. No. 7,202,219 teaches a method for selectively inducing production of butyrate by bacteria in the colon of a human in need thereof by administering TAG. Butyrate is reported to allegedly have a colon cancer protective effect.
Stilbenes and stilbenoids are diarylethenes, stilbenoids being hydroxylated derivatives of stilbenes. Stilbenes and stilbenoids can be found naturally in berries and in the heart wood of the Indian Kino tree, a known medicinal plant in India. Stilbenes have the basic empirical formula of C14H12. A common stilbenoid is resveratrol, also known as 3,5,4′-trihydroxystilbene, a natural component found in the skin of red grapes. Resveratrol is an off-white powdery substance when extracted with methanol and has a molecular weight of 228.24 and an empirical formula of C14H12O3. Resveratrol has been reported to improve health and longevity of mice on high calorie diets under certain circumstances (Baur, J. A., et al., “Resveratrol improves health and survival of mice on high-calorie diet,” Nature, 444(7117):337-42 (2006)). Pterostilbene, also known as 3,5-dimethoxy-4′-hydroxystilbene, is chemically related to resveratrol and may possess many similar properties. Pterostilbene is a white or off-white crystal powder and has a molecular weight of 256 and an empirical formula of C16H16O3.
Diabetes, sometimes known as diabetes mellitus, is a group of disorders characterized by an insufficient amount of, or failure to respond properly to, insulin. There are many forms of diabetes including: Type 1, which results from a failure to produce insulin; and Type 2 which results from insulin resistance; gestational diabetes which occurs in pregnant women who have high glucose levels; and various other types including congenital diabetes, steroid diabetes and monogenic diabetes. As a result of the insulin deficiencies, diabetics typically have hyperglycemia and are subject to acute and chromic complications such as ketoacidosis, and nonketotic hyperosmolar coma. Long-term complications include cardiovascular disease, chronic renal failure, retinal damage, nerve damage, microvascular damage and poor circulation and wound healing. Treatment options currently include the use of insulin, diabetic and blood pressure medications, as well as diet and exercise. Blood glucose monitoring is usually an essential part of treatment as hypoglycemia, or abnormally low blood glucose, can occur as a result of diabetes treatment and/or medications. (“Diabetes Overview,” Nat'l Institute of Diabetes and Digestive and Kidney Diseases, NIH, (2006)).
Atherosclerosis is a syndrome in which the walls of arterial blood vessels are thickened, usually as a result of a build-up of fatty materials such as cholesterol. This syndrome can be promoted by the presence of a high amount of low density lipoproteins (“LDLs”) as well as a low amount of high density lipoproteins (“HDLs”) and a high serum triglyceride concentration. Atherosclerotic patients typically have plaques containing macrophage cells that have taken up oxidized LDLs, lipids such as cholesterol and fatty acids, calcium and fibrous connective tissue that build up along artery walls. Over time, narrowing or complete closure of arteries can result, decreasing the amount of blood supply to the organs and tissues the arteries feed. Additionally, an aneurysm may occur as a result of the artery enlarging to compensate for the blockage. This leads to an increased risk of rupture, which can result in a severe hemorrhage. Alternatively, the plaque may rupture and cause the formation of a thrombus, which can rapidly decrease blood flow to an area. Risk factors include having high blood pressure, diabetes, dyslipoproteinemia, smoking, and high C-reactive protein concentrations in the blood. Treatment options include the medicinal intake of statins, niacin, aspirin and cholesterol-lowering drugs as well as lifestyle modifications such as diet and exercise. Sometimes angioplasty is performed where stents may be inserted to expand narrowed arteries. (“Atherosclerosis,” American Heart Association, available at: http://www.americanheart.org/print_presenter.jhtml:jsessionid=FCG5JBCHQDELMCQFCXPSCZQ?identifier=4440 (2009)).
The Centers for Disease Control (CDC) reports that about two-thirds of the adult population in the United States is classified as either overweight or obese, as defined by a body mass index (“BMI”) of >25 kg/m2 or >30 kg/m2, respectively. Obesity and weight gain reportedly have many causes including overeating, genetics, psychological factors, lifestyle, sex, age, medications, distribution of body fat and certain medical conditions including hyperthyroidism, Cushing syndrome, polycystic ovarian syndrome, and Prader-Willi syndrome. Obesity has been reported to increase the likelihood of various diseases and health problems including heart disease, type 2 diabetes, hypertension, stroke, certain types of cancer including breast and colon, gallstones, gout, depression, sleep apnea and osteoarthritis. Treatment reportedly includes dieting, physical exercise, behavior modification and sometimes anti-obesity drugs such as appetite suppressants, and surgery such as malabsorptive procedures and restrictive procedures. Obesity is the second leading cause of preventable deaths in the United States. (“Overweight and Obesity,” Centers for Disease Control and Prevention, available at: http://www.cdc.gov/obesity/index.html, (2009)).
The metabolic syndrome is characterized by a group of factors and lab test results, which have been alleged to include obesity, weight gain, atherogenic dyslipidemia, especially lower than normal levels of high-density lipoprotein (HDL) cholesterol, hypertension, high serum triglyceride levels (≧150 mg/dl), hypertension, insulin resistance or glucose intolerance and a proinflammatory state characterized by elevated C-reactive protein in the blood. (Torpy, J. M., et al., “The Metabolic Syndrome,” JAMA, 295(7): 850 (2006)). Genetic predispositions to these risk factors increase the likelihood of developing the metabolic syndrome. People with the metabolic syndrome are reportedly at an increased risk of type 2 diabetes, lipodystrophy and cardiovascular disease, such as coronary heart disease, stroke, and peripheral vascular disease. Typically patients with the metabolic syndrome are overweight or obese. Some environmental factors are reported to contribute to the development of the syndrome, such as a sedentary life-style, smoking, and a high carbohydrate diet. Metabolic syndrome is also sometimes associated with liver and kidney problems as well as polycystic ovary syndrome and cognitive decline in the elderly. Reported treatment can consist of lifestyle changes including diet and exercise, as well as medication to treat the disease and the symptoms individually.
It is desired to have compositions and methods to prevent or treat the metabolic syndrome and its underlying causes, as well as atherosclerosis, obesity, and diabetes.